A new disease concept, referred to as chronic kidney diseases (CKD), has been proposed in recent years and this concept has attracted attention throughout the world. In order to treat the disease, the reduction or removal of biologically unstable iron (referred to as non-transferrin-bound iron or NTBI), which is the most frequent causation of the CKD, has been clearly determined to be effective. As used herein, the biologically unstable iron (NTBI) refers to iron ion that is not bound to transferrin and has the potential to have a detrimental effect on the body. Thus, biologically unstable iron (NTBI) does not include, for example, ironbound to transferrin (iron ions present in transferrin-iron complex: transferrin-bound iron), storage iron present as ferritin in the liver, spleen and bone marrow, hemoglobin composed of four heme molecules (porphyrin complex containing iron) and one molecule of globin (comprised of four polypeptide chains) contained in erythrocytes, and myoglobin present in muscle in the form of a chromoprotein that contains a single heme molecule and is stored until oxygen molecules are required for metabolism. Examples of treatment methods for reducing iron in the body, particularly biologically unstable iron (NTBI), or for removing iron outside the body include (1) phlebotomy therapy, (2) low-iron diet therapy, (3) chemotherapy using an iron chelating agent, and (4) blood purification therapy by extracorporeal blood circulation. Phlebotomy therapy is associated with a favorable patient quality of life (QOL), however, since it involves the removal of whole blood, including erythrocytes, it causes adverse side effects such as anemia or hypoproteinemia and can only be applied to patients without anemia. Low-iron diet therapy involves reducing absorption of iron from the digestive tract. It is associated with adverse side effects such as nutritional imbalance, and is only adapted for certain types of liver diseases. Various types of iron chelating agents having potent chemotherapeutic effect have been proposed and mainly used for patients with post-transfusion iron overload (see JP A 2010-31022, WO2009/130604, JP A 2007-532509, JP A 2006-504748, JP A 2005-509649, JP A 2000-507601, JP A 2008-520669, JP A 2002-502816, JP A 2000-506546, JP A 2004-203820, and JP A H9-501144). In iron-related diseases in some organs caused by mild iron overload or iron metabolism abnormalities, there said to be a high frequency of adverse side effects attributable to over-chelation. Moreover, iron chelating agents administered to the body will possibly be incorporated in metabolic processes in vivo, thereby causing an undesirable effect on the body, such as nephropathy. In the case of blood purification therapy by extracorporeal blood circulation, since iron is removed only when blood is circulated outside the body for treatment, there is less likelihood of the occurrence of adverse side effects attributable to over-chelation. The inventors of the present invention have developed an iron chelating agent capable of selectively removing biologically unstable iron (NTBI) which can be used in blood purification therapy (see WO 2010/32489). Even in the case of the iron chelating agent capable of selectively removing biologically unstable iron (NTBI) described in WO 2010/32489, the iron chelating agent dissolved in water will potentially be incorporated into blood and integrated into the metabolic processes in vivo, resulting in an undesirable effect on the body in the same manner as the previously described chelating agents.
JP A H9-501144 describes insolubilized iron-binding polymers that have the effect of lowering absorption of food-derived heme iron and free iron from the gastrointestinal tract. In all of the polymers disclosed in JP A H9-501144, the iron chelating sites are attached to the polymer through —CO—NH— (acrylamide) bond. The iron chelating sites will be lost due to hydrolysis when the polymers are used for extracorporeal blood circulation and come in direct contact with blood, resulting in the potential for having an undesirable effect on the body. In addition, a material for removing heme iron is used in blood purification therapy by extracorporeal blood circulation, there is a high likelihood of inducing anemia, and as such, these polymers are considered to be undesirable.
Patent Document 1: JP A 2010-31022
Patent Document 2: WO 2009/130604
Patent Document 3: JP A 2007-532509
Patent Document 4: JP A 2006-504748
Patent Document 5: JP A 2005-509649
Patent Document 6: JP A 2000-507601
Patent Document 7: JP A 2008-520669
Patent Document 8: JP A 2002-502816
Patent Document 9: JP A 2000-506546
Patent Document 10: JP A 2004-203820
Patent Document 11: JP A H9-501144
Patent Document 12: WO 2010/32489